Our present understanding of pain mechanisms is based primarily on experimental investigations of cutaneous pain. Less well understood are mechanisms of deep pain arising from joints, muscle and particularly the viscera. These latter sources of pain are generally more important clinically than cutaneous pain, but we know less about their mechanisms and control. Foremost among factors that have frustrated investigations of deep pain mechanisms are understanding and defining the adequate stimulus and development of models suitable for quantitative studies. This project has focused over the past several years on visceral pain, developing a reliable model that utilizes a natural, adequate, noxious stimulus, colorectal distension (CRD). Experiments proposed for the next project period will further investigate the modulation of visceral nociception and expand to focus also on afferents from the colon, spinal cellular mechanisms and supraspinal representation of visceral pain. Specific aims include: (1) continuing characterization of modulation of the pressor and visceromotor responses to noxious CRD; (2) quantitative characterization of responses of myelinated and unmyelinated pelvic nerve sensory afferents in the sacral dorsal roots to CRD; (3) an intracellular analysis of the cellular and membrane properties of spinal units that respond to CRD; and (4) characterization of visceral nociceptive unit responses supraspinally in lateral and medial thalamus, the lateral parabrachial area and the rostral, dorsal medulla. These specific aims are a logical extension of the current project and will continue important investigations into the mechanisms of visceral pain and its modulation. The proposed experiments comprise a quantitative, parametric examination of the afferent, spinal and supraspinal physiology and local pharmacological and descending modulation of visceral nociception that will lead to better understanding of the mechanisms and control of visceral pain.